Viral Diseases

1. Viral Diseases Victor Politi, MD,FACP Medical Director, SVCMC School of Allied Health Professions, Physician Assistant Program

2. Introduction • In 1898, Friedrich Loeffler and Paul Frosch found evidence that the cause of foot-and-mouth disease in livestock was an infectious particle smaller than any bacteria. • This was the first clue to the nature of viruses, genetic entities that lie somewhere in the grey area between living and non-living states. Friedrich Loeffler

3. Introduction • Viruses depend on the host cells that they infect to reproduce. • When found outside of host cells, viruses exist as a protein coat or capsid, sometimes enclosed within a membrane. • The capsid encloses either DNA or RNA which codes for the virus elements.

4. Introduction • When it comes into contact with a host cell, a virus can insert its genetic material into its host, literally taking over the host's functions. • An infected cell produces more viral protein and genetic material instead of its usual products.

5. Introduction • Some viruses may remain dormant inside host cells for long periods, causing no obvious change in their host cells (a stage known as the lysogenic phase)

6. Lysogenic cycle In the lysogenic cycle, the virus reproduces by first injecting its genetic material, indicated by the red line, into the host cell's genetic instructions.

7. Lytic Phase • But when a dormant virus is stimulated, it enters the lytic phase: new viruses are formed, self-assemble, and burst out of the host cell, killing the cell and going on to infect other cells.

8. Lytic phase/cycle In the lytic cycle, The virus reproduces itself using the host cell's chemical machinery. The red spiral lines in the drawing indicate the virus's genetic material. The orange portion is the outer shell that protects it.

9. Transduction • Viruses also carry out natural "genetic engineering": a virus may incorporate some genetic material from its host as it is replicating, and transfer this genetic information to a new host, even to a host unrelated to the previous host. • This is known as transduction, and in some cases it may serve as a means of evolutionary change - although it is not clear how important an evolutionary mechanism transduction actually is.

10. Viruses cause a number of diseases in eukaryotes. • In humans, smallpox, the common cold, chickenpox, influenza, shingles, herpes, polio, rabies, Ebola, hanta fever, and AIDS are examples of viral diseases. • Even some types of cancer -- though definitely not all -- have been linked to viruses.

11. Virus particles are about one-millionth of an inch (17 to 300 nanometers) long. • Viruses are about a thousand times smaller than bacteria, and bacteria are much smaller than most human cells. • Viruses are so small that most cannot be seen with a light microscope, but must be observed with an electron microscope.

12. Relative size of viruses and bacteria     

13. Relative size of DNA viruses 

14. Relative size of positive strand RNA viruses 

15. Relative size of negative strand RNA viruses

16. The internationally agreed system of virus classification is based on the structure/composition of the virus particle (virion) • In some cases, the mode of replication is also important in classification. • Viruses are classified into various families on this basis.

17. A virus particle, or virion, consists of the following: • Nucleic acid - either DNA or RNA, either single-stranded or double-stranded • Coat of protein - Surrounds the DNA or RNA to protect it • Lipid membrane - Surrounds the protein coat (found only in some viruses, including influenza; these types of viruses are called enveloped viruses as opposed to naked viruses)

18. Viruses can exist for a long time outside the body. • The way that viruses spread is specific to the type of virus. They can be spread through the following means: • Carrier organisms – mosquitoes,ticks, fleas • The air • Direct transfer of body fluids from one person to another - saliva, sweat, nasal mucus, blood, semen, vaginal secretions • Surfaces on which body fluids have dried

20. Papillomaviruses • Papilloma viruses are wart-causing viruses that cause human neoplasms • Warts are usually benign but can convert to malignant carcinomas. • This occurs in patients with epidermodysplasia verruciformis. • Papilloma viruses are also found associated with human penile, uterine and cervical carcinomas and are very likely to be their cause.

21. Epidermodysplasia verruciformis • This widespread, markedly pruritic, erythematous eruption was eventually found to be caused by human papillomavirus infection.

22. Papillomaviruses • There are 51 types of papilloma viruses • Not all are associated with cancers; however, papillomas may cause 16% of female cancers worldwide and 10% of all cancers. Papilloma virus

23. Papillomaviruses • Vulvar, penile and cervical cancers are associated with type 16 and type 18 papilloma viruses. • The most common genital human papilloma viruses (HPV) aretypes 6 and 11.

24. Human polyoma viruses • This virus causes progressive multifocal leukoencephalopathy ,a disease associated with immunosuppression. • In 1979, the rate of occurrence of this disease was 1.5 per 10 million population. • It has become much more common because of AIDS and is seen in 5% of AIDS patients.

25. Herpes Viruses • Herpes viruses are a leading cause of human viral disease, second only to influenza and cold viruses. • They are capable of causing overt disease or remaining silent for many years only to be reactivated, for example as shingles.

26. Herpes Viruses • The name herpes comes from the Latin herpes which, in turn, comes from the Greek word herpein which means to creep. • This reflects the creeping or spreading nature of the skin lesions caused by many herpes virus types.

27. Human Herpes viruses • Herpes simplex virus (HSV) type 1 • HSV type 2 • Varicella zoster virus (type 3) • Epstein-barr (EB) infectious mononucleosis virus (type 4) • Cytomegalovirus –CMV type 5 • HHV-6 (causative agent of roseola) • HHV-7 • HHV-8- linked with Kaposi sarcoma

28. Human Herpes viruses • Once a patient has become infected by herpes virus, the infection remains for life. • The initial infection may be followed by latency with subsequent reactivation.

29. Human Herpes viruses • Herpes viruses infect most of the human population and persons living past middle age usually have antibodies to most of the above herpes viruses with the exception of HHV-8.

30. Herpes viruses 1 & 2 • Herpes simplex 1 and 2 are frequently benign but can also cause severe disease. • In each case, the initial lesion looks the same. • A clear vesicle containing infectious virus with a base of red (erythomatous) lesion at the base of the vesicle. • This if often referred to as a 'dewdrop on a rose petal'. • From this pus-containing (pustular), encrusted lesions and ulcers may develop.

31. Herpes viruses 1 & 2 • Affect primarily the oral and genital areas • Disease is typically a manifestation of reactivation • Triggers for clinical reactivation are not well understood

32. Herpes Viruses 1&2 • Herpes simplex type 1 (HSV-1) • Largely involves mouth/oral cavity (herpes labialis) • Can cause urogenital infections • HSV-2 • Most common cause of genital ulcers in developing world

33. HSV-1 • Primary infection may be asymptomatic • Vesicles form moist ulcers after several days • if untreated epithelialize over 1-2 weeks • Recurrences • Tend to be labial • Heal faster • Induced by stress, fever, infection, sunlight

34. HSV-2 • Genital herpes is usually the result of HSV-2 with about 10% of cases being the result of HSV-1. • Primary infection is often asymptomatic but many painful lesions can develop on the glans or shaft of the penis in men and on the vulva, vagina, cervix and perianal region of women Largely involve genital tract

35. Hsv-2 • Typical lesions • Multiple, painful, small, grouped and vesicular

36. HSV- Diagnosis • Usually made on clinical grounds • Viral cultures of vesicular fluid • Direct fluorescent antibody staining of scraped lesions • In serum – can be identified using PCR • Cells may be obtained from the base of the lesion (called a Tzank smear) and histochemistry performed • presence of intranuclear inclusions and multinucleated giant cells supportive of dx of herpes

37. HSV-Clinical Findings • Ocular dx (keratitis, blepharitis, keratoconjunctivitis) • Neonatal & congenital infection • Encephalitis/recurrent meningitis • Disseminated infection • Bell’s Palsy • Esophagitis • Erythema Multiforme

38. Herpes keratitis • This is an infection of the eye and is primarily caused by HSV-1. • It can be recurrent and may lead to blindness. • It is a leading cause of corneal blindness in the United States.

39. Herpes whitlow This disease of persons who come in manual contact with herpes-infected body secretions can be cause by either type of HSV and enters the body via small wounds on the hands or wrists. It can also be caused by transfer of HSV-2 from genitals to the hands

40. HSV encephalitis • This is usually the result of an HSV-1 infection and is the most common sporadic viral encephalitis. • HSV encephalitis is a febrile disease and may result in damage to one of the temporal lobes. • As a result there is blood in the spinal fluid and the patient experiences neurological symptoms such as seizures. • The disease can be fatal but in the US there are fewer than 1000 cases per year.

41. HSV- Treatment/Prevention • Urogenital, encephalitic or disseminated disease • acyclovir & related compounds • Keratitis • trifluridine • Resistant strains in immunocompromised • foscarnet

42. Prevention • Recurrent mucocutaneous disease is most effectively treated with acyclovir • Recurrent genital disease also requires barrier precautions during sexual activity • Asymptomatic transmission occurs – especially with HSV-2

43. Chicken Pox Highly contagious Generally dx of childhood Spread by inhalation of infected droplets or contact with lesions after 10-20 days Fever/malaise mild in children Pruritic rash evolves centrifugally – beginning on face/scalp/trunk – lesser degree on extremities Shingles After primary infection virus remains dormant in nervous tissue Pain often severe, may precede rash Lesions follow any nerve root distribution – typically thoracic & lumbar Ramsay Hunt Syndrome – geniculate ganglion involvement Varicella & Herpes Zoster Chicken pox or shingles (its reactivation)

44. Typical isolated rash in shingles • In severe cases of shingles, the lesions coalesce, forming a disfiguring carpet of scabs and sometimes the rash leaves permanent scars

45. Varicella & Herpes Zoster Chicken pox or shingles (its reactivation) • Varicella Complications – • Interstitial pneumonia • more common in adults than children • Hepatitis • Reye’s syndrome • Usually in childhood/associated with aspirin use • Congenital malformation • congenital varicella syndrome which leads to scarring of the skin of the limbs, damage to the lens, retina and brain and microphthalmia • Secondary bacterial infection • Group A beta-hemolytic streptococci common

47. Varicella & Herpes Zoster Chicken pox or shingles (its reactivation) • Herpes Zoster • Postherpetic neuralgia • Occurs in 60-70% of patients > age 60 • Encephalitis, skin lesions beyond the dermatome, and visceral lesions • Seen in immunocompromised & HIV patients

48. Epstein- Barr Virus     Epstein-Barr virus is the causative agent of Burkitt's lymphoma in Africa, nasal pharyngeal carcinoma in the orient and infectious mononucleosis in the west.

49. EBV • Why this virus causes a benign disease in some populations but malignant disease in others is unknown. Burkitt's Lymphoma caused by Epstein-Barr Virus 

50. Infectious mononucleosis • The primary infection is often asymptomatic. • Some patients develop infectious mononucleosis after 1-2 months of infection. • The disease is characterized by malaise, lymphadenopathy, tonsillitis, enlarged spleen and liver and fever. • The fever may persist for more than a week. • There may also be a rash. • The severity of disease often depends on age (with younger patients resolving the disease more quickly) and resolution usually occurs in 1 to 4 weeks.